Clonal succession after prolonged antiretroviral therapy rejuvenates CD8 T cell responses against HIV-1.

Human immunodeficiency virus 1 (HIV-1) infection is characterized by a dynamic and persistent state of viral replication that overwhelms the host immune system in the absence of antiretroviral therapy (ART). The impact of prolonged treatment on the antiviral efficacy of HIV-1-specific CD8 T cells has nonetheless remained unknown. Here, we used single-cell technologies to address this issue in a cohort of aging individuals infected early during the pandemic and subsequently treated with continuous ART.

Comparison of HIV-Infected and Noninfected Patients Undergoing Bariatric Surgery: The ObeVIH Study.

Objective: The aim of this study was to compare clinical characteristics and adipose/liver tissue histology analysis in HIV-infected and HIV-uninfected subjects undergoing bariatric surgery.

Design: This was a cross-sectional study of HIV-infected subjects undergoing single-port sleeve gastrectomy with prospective enrolment and frequency age (±5 years), sex, and body mass index (BMI, ± 5 kg/m2) matched on HIV-uninfected subjects.

Methods: This study was conducted at a single clinical site at Pitié-Salpêtrière hospital-Paris-France comprising 19 HIV-uninfected and 21 HIV-infected subjects with plasma VL < 20 copies/mL, all with a BMI > 40 kg/m2 or >35 kg/m2 with comorbidities.

Household transmission of SARS-CoV-2 infection in the Paris/Ile-de-France area.

This st udy aims to evaluate the prevalence of SARS-CoV-2 antibodies in locked-down family households to determine viral dynamics and immunity acquisition. COVID-19 individuals and their households in lockdown under the same roof during early spring 2020 were interviewed and tested using rapid immunochromatographic lateral flow antibodies assays (LFA) between July and September 2020. Outcomes were secondary infection rate (SIR) among contacts, household infection rate, and predictors of transmission.

Prevalence and factors associated with symptom persistence: A prospective study of 429 mild COVID-19 outpatients.

Introduction: Persistent symptoms have recently emerged as a clinical issue in COVID-19. We aimed to assess the prevalence and risk factors in symptomatic non-hospitalized individuals with mild COVID-19.

Methods: We performed a prospective cohort study of symptomatic COVID-19 outpatients, from March to May 2020, with weekly phone calls from clinical onset until day 30 and up to day 60 in case of persistent symptoms.

Olfactory and gustatory dysfunctions in COVID-19 outpatients: A prospective cohort study.

Objectives: To describe the characteristics, evolution and risk factors for long-term persistence of olfactory and gustatory dysfunctions (OGD) in COVID-19 outpatients.

Patients And Methods: We conducted a prospective study in SARS-CoV-2 infected outpatients with OGD. Weekly phone interviews were set up starting from COVID-19 onset symptoms and over the course of 60 days, using standardized questionnaires that included a detailed description of general symptoms and OGD.

Once-daily etravirine/raltegravir (400/800 mg q24h) dual therapy maintains viral suppression over 48 weeks in HIV-infected patients switching from a twice-daily etravirine/raltegravir (200/400 mg q12h) regimen.

Background: Etravirine/raltegravir dual therapy has been shown to be highly effective as a twice-daily (q12h) regimen in suppressed HIV-infected patients enrolled in the ANRS-163 study.

Objectives: As a once-daily (q24h) regimen is easier for daily life, we aimed to evaluate the capacity of etravirine/raltegravir (400/800 mg) q24h to maintain viral suppression in patients on etravirine/raltegravir q12h.

Methods: Patients on a suppressive etravirine/raltegravir q12h regimen for at least 96 weeks were switched to etravirine/raltegravir q24h in this prospective, multicentre, open-label, single-arm study.

HIV therapeutic vaccine enhances non-exhausted CD4 T cells in a randomised phase 2 trial.

VAC-3S is a therapeutic vaccine comprising a highly conserved HIV-gp41 motif coupled with the CRM197 carrier protein. High levels of anti-3S antibodies (Abs) have been associated with improved protection of CD4 T-cell survival. A previous phase 1 study demonstrated the safety of VAC-3S.

Routine screening for HIV, hepatitis B virus and hepatitis C virus in individuals undergoing oral and maxillofacial surgery.

Objectives: Given the effectiveness of treatment of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, there are considerable benefits associated with determining HIV/HBV/HCV status. We evaluated the feasibility and acceptability of systematic screening and subsequent care in an oral and maxillofacial surgery department.

Methods: The anaesthesiologists proposed screening for HIV, HBV and HCV to all individuals of unknown infection status undergoing surgery between 19 April 2016 and 19 April 2017.

Treatment interruption in chronically HIV-infected patients with an ultralow HIV reservoir.

Objectives: To investigate the potential for combination antiretroviral therapy (cART)-free remission following analytic treatment interruption (ATI) in chronically HIV-infected patients with ultralow cell-associated DNA.

Methods: Pilot study of patients (pts) with plasma viral load (pVL) less than 50 copies/ml for more than 2 years on cART, CD4 above 500 cells/μl, CD4/CD8 above 0.9, CD4 nadir above 300 cells/μl and HIV-DNA below 100 copies/10 peripheral blood mononuclear cells (PBMCs), undergoing treatment interruption.

Vitamin D supplementation is associated with reduced immune activation levels in HIV-1-infected patients on suppressive antiretroviral therapy.

Background: A majority of HIV-1-infected patients present a severe deficit in vitamin D, which predicts short-term mortality. Vitamin D is a naturally synthesized hormone, with important immunomodulatory functions. In the general population, its deficit has been associated with increased markers of inflammation.

Neutrophils in antiretroviral therapy-controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment.

Background: Despite control of HIV infection under antiretroviral therapy (ART), immune T-cell activation persists in patients with controlled HIV infection, who are at higher risk of inflammatory diseases than the general population. PMNs play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in cases of excessive or misdirected responses.

Objective: The aim of our study was to analyze PMN functions in 60 ART-treated and controlled HIV-infected patients (viral load, <20 RNA copies/mL; CD4 count, ≥ 350 cells/mm(3)) with (HIV[I] group) and without (HIV[NI] group) diseases related to an inflammatory process and to compare them with 22 healthy control subjects.

Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia.

Background: Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not known whether patients able to secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia [PHG]).

Objective: This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome.

Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies.

Lifelong immunoglobulin replacement is the standard, expensive therapy for severe primary antibody deficiencies. This treatment can be administrated either by intravenous immunoglobulin (IVIG) or subcutaneous infusions (SCIG) and delivered at home or in an out-patient setting. This study aims to determine whether SCIG is cost-effective compared with IVIG from a French social insurance perspective.

The European internet-based patient and research database for primary immunodeficiencies: results 2006-2008.

Primary immunodeficiencies (PID) are rare diseases; therefore transnational studies are essential to maximize the scientific outcome and to improve diagnosis and therapy. In order to estimate the prevalence of PID in Europe as well as to establish and evaluate harmonized guidelines for the diagnosis and treatment of PID, the European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This database is a platform for epidemiological analyses as well as the development of new diagnostic and therapeutic strategies and the identification of novel disease-associated genes.

A natural CCL5/RANTES variant antagonist for CCR1 and CCR3.

The N-terminal domain of the chemokine CCL5/regulated upon activation normal T cell expressed and secreted (RANTES) has been shown to be critical for its biological activity on leukocytes. Several N-terminus-modified CCL5/RANTES derivatives, such as N-Terminal truncated CCL5/RANTES, Met-RANTES, and amino-oxypentane (AOP)-RANTES exhibited antagonist or partial agonist functions when investigated on the properties of their receptors CCR1, CCR3, and CCR5. Studying 95 African samples from Cameroon, we found a naturally occurring variant of CCL5/RANTES containing a missense mutation located in the first amino acid of the secreted form (S24F).

Polymorphism in the proximal promoter region of the perforin gene and its impact on the course of HIV infection.

Cytotoxic T lymphocytes (CTLs) play an essential role in the control of viral replication during human immunodeficiency virus (HIV) infection. However, the efficacy of the CTL response varies between individuals. We tested the hypothesis that genetic polymorphisms in the lytic effector molecule perforin could influence the progression of HIV infection.

Influence of the R22H variant of macrophage inflammatory protein 1beta/Lag-1 in HIV-1 survival.

The chemokine macrophage inflammatory protein 1beta/CCL4, ligand of the major HIV co-receptor CCR5, is encoded by two genes, Act-2 and Lag-1. Our work focused on R22H, a variant of Lag-1 located near the N-loop, in the 310 turn, a domain essential for interacting with CCR5. We observed that HIV-1-infected patients from the SEROCO cohort, bearing the R22H variant either at the homozygous or heterozygous state, exhibit a worse global survival compared with wild-type homozygous individuals.

Biochemical and HIV-1 coreceptor properties of K26R, a new CCR5 Variant in China's Sichuan population.

Despite multiple exposures to HIV-1, some individuals remain uninfected. This resistance to HIV infection has been associated with homozygosity for a 32-basepair deletion in the CCR5 receptor gene. This variant is frequent in caucasians but extremely rare in Asians and Africans.

32-nucleotide deletion, associated with defence against hiv/aids, is a predominant mutation of CCR5 gene in the population of Georgia.

There is a special interest to investigate genetic peculiarities in the populations with a low HIV seroprevalence. Despite of presence of high-risk conditions for rapid spread of HIV/AIDS epidemics in Georgia, the prevalence of this infection in the country remains very low. We studied polymorphisms of CCR5 gene in Georgians.

New CCR5 variants associated with reduced HIV coreceptor function in southeast Asia.

Background: Despite multiple exposure to HIV-1, some individuals remain uninfected. This resistance has been associated with homozygosity for a 32 base pair deletion in the gene for the CCR5 receptor. This variant occurs frequently in Caucasians but is extremely rare in Asians or Africans.

A triple-mutated allele of granzyme B incapable of inducing apoptosis.

Granzyme B (GzmB) is a serine protease involved in many pathologies, including viral infections, autoimmunity, transplant rejection, and antitumor immunity. To measure the extent of genetic variation in GzmB, we screened the GzmB gene for polymorphisms and defined a frequently represented triple-mutated GzmB allele. In this variant, three amino acids of the mature protein Q(48)P(88)Y(245) are mutated to R(48)A(88)H(245).

HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize in white pulps and germinal centers from infected patients.

Human immunodeficiency virus (HIV) infection is characterized by the massive infiltration of secondary lymphoid organs with activated CD8(+) T lymphocytes. While converging data indicated that these cells were HIV-specific cytotoxic T lymphocytes (CTLs) responsible for HIV spread limitation, direct evidence was lacking. Here, the presence of HIV-specific effector CTLs was demonstrated directly ex vivo in 15 of 24 microdissected splenic white pulps from an untreated patient and in 1 of 24 tonsil germinal centers from a second patient with incomplete viral suppression following bitherapy.

Dynamics of viral variants in HIV-1 Nef and specific cytotoxic T lymphocytes in vivo.

The vigorous CTL response directed against HIV is considered to be important in reducing HIV viral load, although it is unable to stop ongoing viral replication, which generates new antigenic variants. We analyzed the impact of sequential changes in five epitopes of HIV-1 Nef on CTL recognition in four stable patients. A high rate of variation was found, and in all these patients we could detect CTL specific for 32 out of 36 autologous viral variants occurring in 5 HLA-A2- or HLA-B7-restricted Nef epitopes at two time points.

A novel mode of human immunodeficiency virus type 1 (HIV-1) activation: ligation of CD28 alone induces HIV-1 replication in naturally infected lymphocytes.

Induction of human immunodeficiency virus (HIV) replication in infected CD4+ T lymphocytes requires cellular activation. The ligation of CD28, a signal-transducing receptor with a natural ligand on activated B cells and antigen-presenting cells, provides a costimulating signal for interleukin 2 production and T-cell proliferation as well as coactivation of the transfected HIV long terminal repeat in Jurkat cells. The aim of the present study was to investigate the ability of CD28 ligation to activate HIV type 1 (HIV-1) replication in naturally infected CD4+ lymphocytes either alone or in combination with immobilized anti-CD3 monoclonal antibody.